Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs Journal Article

   

Authors:	Hadi, K.; Yao, X.; Behr, J. M.; Deshpande, A.; Xanthopoulakis, C.; Tian, H.; Kudman, S.; Rosiene, J.; Darmofal, M.; DeRose, J.; Mortensen, R.; Adney, E. M.; Shaiber, A.; Gajic, Z.; Sigouros, M.; Eng, K.; Wala, J. A.; Wrzeszczyński, K. O.; Arora, K.; Shah, M.; Emde, A. K.; Felice, V.; Frank, M. O.; Darnell, R. B.; Ghandi, M.; Huang, F.; Dewhurst, S.; Maciejowski, J.; de Lange, T.; Setton, J.; Riaz, N.; Reis-Filho, J. S.; Powell, S.; Knowles, D. A.; Reznik, E.; Mishra, B.; Beroukhim, R.; Zody, M. C.; Robine, N.; Oman, K. M.; Sanchez, C. A.; Kuhner, M. K.; Smith, L. P.; Galipeau, P. C.; Paulson, T. G.; Reid, B. J.; Li, X.; Wilkes, D.; Sboner, A.; Mosquera, J. M.; Elemento, O.; Imielinski, M.
Article Title:	Distinct classes of complex structural variation uncovered across thousands of cancer genome graphs
Abstract:	A novel computational approach for inferring and classifying patterns in cancer genome graphs uncovers three classes of complex structural variation with distinct tumor type and genomic distributions. © 2020 Elsevier Inc. Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are “towers” of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise “chasms” of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are “typhoons” of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis. © 2020 Elsevier Inc.
Keywords:	human tissue; protein expression; gene mutation; major clinical study; gene deletion; dna repair; ovary cancer; breast cancer; cohort analysis; genetic association; genetic variation; mathematical model; gene rearrangement; pilot study; gene fusion; gene duplication; gene dosage; genetic code; aneuploidy; cancer genomics; gene replication; cancer evolution; gastrointestinal carcinoma; cancer prognosis; chromothripsis; structural variation; mutational processes; human; male; priority journal; article; whole genome sequencing; oncogenomics; fragile sites; genome graphs; phasing; superenhancers
Journal Title:	Cell
Volume:	183
Issue:	1
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2020-10-01
Start Page:	197
End Page:	210.e32
Language:	English
DOI:	10.1016/j.cell.2020.08.006
PUBMED:	33007263
PROVIDER:	scopus
PMCID:	PMC7912537
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091663377&doi=10.1016%2fj.cell.2020.08.006&partnerID=40&md5=83fa0d5cd0e5eabf8b9073a2a843e6d2
Notes:	Article -- Export Date: 2 November 2020 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/172022